Trans‐[Ru(NO)(NH3)4(py)](BF4)3 encapsulated in PLGA nano and microparticles for delivery of nitric oxide to neoplasic cells

Abstract

The NO donor trans‐[Ru(NO)(NH3)4(py)](BF4)3 was loaded into poly‐lactic‐co‐glycolic acid (PLGA) particles (pyMP) and the ability of pyMP to deliver NO was tested on the cultured B16‐F10, melan‐a and WM1552 melanoma cells. Scanning electron microscopy and dynamic light scattering revealed that the particles are spherical, have a diameter of 200 to 1200 nm. The complex in solution, in the absence of irradiation, is toxic at higher concentrations (1×10−3 mol.L−1) with cell death attributed to NO release following reduction of the complex in the cell environment. There was no cell death with pyMP, due to the lower bioavailability and availability of the entrapped complex to the medium and its reducing agents. Upon light irradiation, pyMP is able to release sufficient NO that can diffuse out of the matrix, reach the adjacent cell membranes, and kill the tumor cells. The phototoxicity strongly suggests that cell death is due to NO release from trans‐[Ru(NO)(NH3)4(py)]3+. Supported by FAPESP (05/58170‐2), CNPq (151406/2007‐3).